{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T07:12:56Z","timestamp":1761808376652,"version":"3.37.3"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100008894","name":"Stryker","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Trauma Emerg Surg"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1007\/s00068-020-01407-z","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T21:02:30Z","timestamp":1590440550000},"page":"1491-1497","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Soluble terminal complement activation fragment sC5b-9: a new serum biomarker for traumatic brain injury?"],"prefix":"10.1007","volume":"47","author":[{"given":"Joshua","family":"Parry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiho","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cedric F.","family":"Stahel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corey","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Nadeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Stacey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Beauchamp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest E.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip F.","family":"Stahel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"1407_CR1","first-page":"167","volume":"116","author":"M Maegele","year":"2019","unstructured":"Maegele M, Lefering R, Sakowitz O, Kopp MA, Schwab JM, Steudel WI, Unterberg A, Hoffmann R, Uhl E, Marzi I. The incidence and management of moderate to severe head injury. Dtsch Arztebl Int. 2019;116:167\u201373.","journal-title":"Dtsch Arztebl Int"},{"key":"1407_CR2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.imbio.2015.11.011","volume":"221","author":"T Lustenberger","year":"2016","unstructured":"Lustenberger T, Kern M, Relja B, Wutzler S, Stormann P, Marzi I. The effect of brain injury on the inflammatory response following severe trauma. Immunobiology. 2016;221:427\u201331.","journal-title":"Immunobiology"},{"key":"1407_CR3","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s00068-004-1394-9","volume":"30","author":"OI Schmidt","year":"2004","unstructured":"Schmidt OI, Infanger M, Heyde CE, Ertel W, Stahel PF. The role of neuroinflammation in traumatic brain injury. Eur J Trauma. 2004;30:135\u201349.","journal-title":"Eur J Trauma"},{"key":"1407_CR4","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/S0165-0173(98)00015-0","volume":"27","author":"PF Stahel","year":"1998","unstructured":"Stahel PF, Morganti-Kossmann MC, Kossmann T. The role of the complement system in traumatic brain injury. Brain Res Rev. 1998;27:243\u201356.","journal-title":"Brain Res Rev"},{"key":"1407_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12974-018-1066-z","volume":"15","author":"A Hammad","year":"2018","unstructured":"Hammad A, Westacott L, Zaben M. The role of the complement system in traumatic brain injury: a review. J Neuroinflammation. 2018;15:24.","journal-title":"J Neuroinflammation"},{"key":"1407_CR6","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1089\/neu.2017.5168","volume":"35","author":"F Roselli","year":"2018","unstructured":"Roselli F, Karasu E, Volpe C, Huber-Lang M. Medusa's head: the complement system in traumatic brain and spinal cord injury. J Neurotrauma. 2018;35:226\u201340.","journal-title":"J Neurotrauma"},{"key":"1407_CR7","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0165-5728(96)00164-6","volume":"73","author":"T Kossmann","year":"1997","unstructured":"Kossmann T, Stahel PF, Morganti-Kossmann MC, Jones JL, Barnum SR. Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury. J Neuroimmunol. 1997;73:63\u20139.","journal-title":"J Neuroimmunol"},{"key":"1407_CR8","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1089\/08977150152725605","volume":"18","author":"BM Bellander","year":"2001","unstructured":"Bellander BM, Singhrao SK, Ohlsson M, Mattsson P, Svennson M. Complement activation in the human brain after traumatic brain injury. J Neurotrauma. 2001;18:1295\u2013311.","journal-title":"J Neurotrauma"},{"key":"1407_CR9","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/jcbfm.1995.107","volume":"15","author":"SL Kaczorowksi","year":"1995","unstructured":"Kaczorowksi SL, Schiding JK, Toth CA, Kochanek PM. Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. J Cereb Blood Flow Metab. 1995;15:860\u20134.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1407_CR10","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1097\/01.WCB.0000084250.20114.2C","volume":"23","author":"M Rancan","year":"2003","unstructured":"Rancan M, Morganti-Kossmann MC, Barnum SR, Saft S, Schmidt OI, Ertel W, Stahel PF. Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice. J Cereb Blood Flow Metab. 2003;23:1070\u20134.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1407_CR11","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.expneurol.2006.01.033","volume":"199","author":"I Leinhase","year":"2006","unstructured":"Leinhase I, Schmidt OI, Thurman JM, Hossini AM, Rozanski M, Taha ME, Scheffler A, John T, Smith WR, Holers VM, Stahel PF. Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Exp Neurol. 2006;199:454\u201364.","journal-title":"Exp Neurol"},{"key":"1407_CR12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/1471-2202-7-55","volume":"7","author":"I Leinhase","year":"2006","unstructured":"Leinhase I, Holers VM, Thurman JM, Harhausen D, Schmidt OI, Pietzcker M, Taha ME, Rittirsch D, Huber-Lang M, Smith WR, Ward PA, Stahel PF. Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. BMC Neurosci. 2006;7:55.","journal-title":"BMC Neurosci"},{"key":"1407_CR13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1742-2094-4-13","volume":"4","author":"I Leinhase","year":"2007","unstructured":"Leinhase I, Rozanski M, Harhausen D, Thurman JM, Schmidt OI, Hossini AM, Taha ME, Rittirsch D, Ward PA, Holers VM, Ertel W, Stahel PF. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice. J Neuroinflamm. 2007;4:13.","journal-title":"J Neuroinflamm"},{"key":"1407_CR14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1742-2094-6-2","volume":"6","author":"PF Stahel","year":"2009","unstructured":"Stahel PF, Flierl MA, Morgan BP, Persigehl I, Stoll C, Conrad C, Touban BM, Smith WR, Beauchamp K, Schmidt OI, Ertel W, Leinhase I. Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. J Neuroinflamm. 2009;6:2.","journal-title":"J Neuroinflamm"},{"key":"1407_CR15","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1423-0127-18-90","volume":"18","author":"MD Neher","year":"2011","unstructured":"Neher MD, Weckbach S, Flierl MA, Huber-Lang MS, Stahel PF. Molecular mechanisms of inflammation and tissue injury after major trauma - is complement the \"bad guy\"? J Biomed Sci. 2011;18:90.","journal-title":"J Biomed Sci"},{"key":"1407_CR16","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1089\/089771501316919139","volume":"18","author":"PF Stahel","year":"2001","unstructured":"Stahel PF, Morganti-Kossmann MC, Perez D, Redaelli C, Gloor B, Trentz O, Kossmann T. Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury. J Neurotrauma. 2001;18:773\u201381.","journal-title":"J Neurotrauma"},{"key":"1407_CR17","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.atherosclerosis.2008.07.044","volume":"204","author":"G Szeplaki","year":"2009","unstructured":"Szeplaki G, Szegdei R, Hirschberg K, Gombos T, Varga L, Karadi I, Entz L, Szeplaki Z, Garred P, Prohaszka Z, Fust G. Strong complement activation after acute ischemic stroke is associated with unfavorable outcomes. Atherosclerosis. 2009;204:315\u201320.","journal-title":"Atherosclerosis"},{"key":"1407_CR18","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1097\/shk.0b013e3180342439","volume":"28","author":"MT Ganter","year":"2007","unstructured":"Ganter MT, Brohi K, Cohen MJ, Shaffer LA, Walsh MC, Stahl GL, Pittet JF. Role of the alternative pathway in the early complement activation following major trauma. Shock. 2007;28:29\u201334.","journal-title":"Shock"},{"key":"1407_CR19","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1097\/SHK.0b013e3182471795","volume":"37","author":"AM Burk","year":"2012","unstructured":"Burk AM, Martin M, Flierl MA, Rittirsch D, Helm M, Lampl L, Bruckner U, Stahl GL, Blom AM, Perl M, Gebhard F, Huber-Lang M. Early complementopathy after multiple injuries in humans. Shock. 2012;37:348\u201354.","journal-title":"Shock"},{"key":"1407_CR20","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/SMJ.0000000000000086","volume":"107","author":"MD Neher","year":"2014","unstructured":"Neher MD, Keene CN, Rich MC, Moore HB, Stahel PF. Serum biomarkers for traumatic brain injury. South Med J. 2014;107:248\u201355.","journal-title":"South Med J"},{"key":"1407_CR21","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.3389\/fimmu.2018.02050","volume":"9","author":"S Chakraborty","year":"2018","unstructured":"Chakraborty S, Karasu E, Huber-Lang M. Complement after trauma: suturing innate and adaptive immunity. Front Immunol. 2018;9:2050.","journal-title":"Front Immunol"},{"key":"1407_CR22","doi-asserted-by":"crossref","first-page":"861","DOI":"10.4049\/jimmunol.159.2.861","volume":"159","author":"PF Stahel","year":"1997","unstructured":"Stahel PF, Frei K, Eugster HP, Fontana A, Hummel KM, Wetsel RA, Ames RS, Barnum SR. TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis. J Immunol. 1997;159:861\u20139.","journal-title":"J Immunol"},{"key":"1407_CR23","first-page":"897","volume":"151","author":"PF Stahel","year":"1997","unstructured":"Stahel PF, Frei K, Fontana A, Eugster HP, Ault BH, Barnum SR. Evidence for intrathecal synthesis of alternative pathway complement activation proteins in experimental meningitis. Am J Pathol. 1997;151:897\u2013904.","journal-title":"Am J Pathol"},{"key":"1407_CR24","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0169-328X(97)00189-7","volume":"50","author":"PF Stahel","year":"1997","unstructured":"Stahel PF, Kossmann T, Morganti-Kossmann MC, Hans VH, Barnum SR. Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Mol Brain Res. 1997;50:205\u201312.","journal-title":"Mol Brain Res"},{"key":"1407_CR25","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/S0165-5728(00)00304-0","volume":"109","author":"PF Stahel","year":"2000","unstructured":"Stahel PF, Kariya K, Shohami E, Barnum SR, Eugster H, Trentz O, Kossmann T, Morganti-Kossmann MC. Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice. J Neuroimmunol. 2000;109:164\u201372.","journal-title":"J Neuroimmunol"},{"key":"1407_CR26","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1586\/1744666X.2.3.445","volume":"2","author":"PF Stahel","year":"2006","unstructured":"Stahel PF, Barnum SR. The role of the complement system in CNS inflammatory diseases. Expert Rev Clin Immunol. 2006;2:445\u201356.","journal-title":"Expert Rev Clin Immunol"},{"key":"1407_CR27","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/j.injury.2007.09.023","volume":"38","author":"PF Stahel","year":"2007","unstructured":"Stahel PF, Smith WR, Moore EE. Role of biological modifiers regulating the immune response after trauma. Injury. 2007;38:1409\u201322.","journal-title":"Injury"},{"key":"1407_CR28","doi-asserted-by":"crossref","unstructured":"Weber B, Lackner I, Knecht D, Braun CK, Gebhard F, Huber-Lang M, Hilderbrand F, Horst K, Pape HC, Ignatius A, Schrezenmeier H, Haffner-Luntzer M, Kalbitz M. Systemic and cardiac alterations after long bone fracture. Shock. 2020 (March 19, Epub ahead of print)","DOI":"10.1097\/SHK.0000000000001536"},{"key":"1407_CR29","doi-asserted-by":"publisher","first-page":"5628","DOI":"10.4049\/jimmunol.0903678","volume":"185","author":"U Amara","year":"2010","unstructured":"Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B, Bruckner UB, Nilsson B, Gebhard F, Lambris JD, Huber-Lang M. Molecular intercommunication between the complement and coagulation systems. J Immunol. 2010;185:5628\u201336.","journal-title":"J Immunol"},{"key":"1407_CR30","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/rth2.12175","volume":"3","author":"M Levi","year":"2019","unstructured":"Levi M, Cohn DM, Zeerleder S. Hereditary angioedema: linking complement regulation to the coagulation system. Res Pract Thromb Haemost. 2019;3:38\u2013433.","journal-title":"Res Pract Thromb Haemost"},{"key":"1407_CR31","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1097\/TA.0000000000002092","volume":"86","author":"CD Barrett","year":"2019","unstructured":"Barrett CD, Moore HB, Kong YW, Chapman MP, Sriram G, Lim D, Moore EE, Yaffe MB. Tranexamic acid mediates proinflammatory and anti-inflammatory signaling via complement C5a regulation in a plasminogen activator-dependent manner. J Trauma Acute Care Surg. 2019;86:101\u20137.","journal-title":"J Trauma Acute Care Surg"},{"key":"1407_CR32","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1742-2094-7-15","volume":"7","author":"D Harhausen","year":"2010","unstructured":"Harhausen D, Khojasteh U, Stahel PF, Morgan BP, Nietfeld W, Dirnagl U, Trendelenburg G. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice. J Neuroinflammation. 2010;7:15.","journal-title":"J Neuroinflammation"},{"key":"1407_CR33","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.tips.2017.03.009","volume":"38","author":"SR Barnum","year":"2017","unstructured":"Barnum SR. Therapeutic inhibition of complement: well worth the risk. Trends Pharmacol Sci. 2017;38:503\u20135.","journal-title":"Trends Pharmacol Sci"},{"issue":"9475","key":"1407_CR34","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1016\/S0140-6736(05)66552-X","volume":"365","author":"P Edwards","year":"2005","unstructured":"Edwards P, Arango M, Balica L, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet. 2005;365(9475):1957\u20139.","journal-title":"Lancet"},{"key":"1407_CR35","doi-asserted-by":"publisher","first-page":"731","DOI":"10.2119\/2008-00050.Beauchamp","volume":"14","author":"K Beauchamp","year":"2008","unstructured":"Beauchamp K, Mutlak H, Smith WR, Shohami E, Stahel PF. Pharmacology of traumatic brain injury: where is the \"golden bullet\"? Mol Med. 2008;14:731\u201340.","journal-title":"Mol Med"},{"issue":"10039","key":"1407_CR36","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/S0140-6736(16)30522-0","volume":"388","author":"PF Stahel","year":"2016","unstructured":"Stahel PF. The inherent dangers of high-dose steroids for acute inflammatory conditions. Lancet. 2016;388(10039):102.","journal-title":"Lancet"},{"key":"1407_CR37","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.trsl.2014.10.010","volume":"165","author":"EK Wong","year":"2015","unstructured":"Wong EK, Kavanagh D. Anticomplement C5 therapy with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Transl Res. 2015;165:306\u201320.","journal-title":"Transl Res"},{"key":"1407_CR38","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.pharmthera.2016.11.014","volume":"172","author":"SR Barnum","year":"2017","unstructured":"Barnum SR. Complement: a primer for the coming therapeutic revolution. Pharmacol Ther. 2017;172:63\u201372.","journal-title":"Pharmacol Ther"},{"key":"1407_CR39","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1097\/BOT.0b013e3181b6bdfc","volume":"24","author":"MA Flierl","year":"2010","unstructured":"Flierl MA, Stoneback JW, Beauchamp KM, Hak DJ, Morgan SJ, Smith WR, Stahel PF. Femur shaft fracture fixation in head-injured patients: when is the right time? J Orthop Trauma. 2010;24:107\u201314.","journal-title":"J Orthop Trauma"},{"key":"1407_CR40","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13017-019-0229-2","volume":"14","author":"E Picetti","year":"2019","unstructured":"Picetti E, Maier RV, Rossi S, Kirkpatrick AW, Biffl WL, Stahel PF, Moore EE, Kluger Y, Baiocchi GL, Ansaloni L, Agnoletti V, Catena F. Preserve encephalus in surgery of trauma: online survey (PESTO). World J Emerg Surg. 2019;14:9.","journal-title":"World J Emerg Surg"}],"container-title":["European Journal of Trauma and Emergency Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00068-020-01407-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00068-020-01407-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00068-020-01407-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T13:03:40Z","timestamp":1696165420000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00068-020-01407-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,25]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["1407"],"URL":"https:\/\/doi.org\/10.1007\/s00068-020-01407-z","relation":{},"ISSN":["1863-9933","1863-9941"],"issn-type":[{"type":"print","value":"1863-9933"},{"type":"electronic","value":"1863-9941"}],"subject":[],"published":{"date-parts":[[2020,5,25]]},"assertion":[{"value":"11 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"P.F.S. is the recipient of a peer-reviewed research grant by Stryker Corporation (Kalamazoo, MI) for this project, and the co-inventor of a United States patent No. 11,441,828 entitled: <i>\u201cInhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury, and related conditions.\u201d<\/i> The other authors declare no conflict of interest related to this project.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study protocol was approved by the Colorado Multiple Institutional Review Board (COMIRB) #10-0638. The IRB protocol allowed a waiver of consent due to minimal risk.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval, consent for participation and publication"}}]}}